Kvansakul Marc, Hinds Mark G
La Trobe Institute for Medical Science, La Trobe University, Bundoora, Victoria, Australia.
School of Chemistry, The University of Melbourne, Parkville, Victoria, Australia; Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
Methods Enzymol. 2014;544:49-74. doi: 10.1016/B978-0-12-417158-9.00003-0.
B-cell lymphoma-2 (Bcl-2) homology-3 (BH3)-only proteins are considered members of the Bcl-2 family, though they bear little sequence or structural identity with the multi-BH motif prosurvival or proapoptotic Bcl-2 proteins like Bcl-2 or Bax. They are better considered a separate phylogenetic entity. In combination, results from biophysical, biochemical, cell biological, and animal studies in conjunction with structural investigations have elucidated the function and mechanism of action of these proteins. Either by antagonizing prosurvival Bcl-2 proteins or directly activating proapoptotic Bcl-2 proteins (Bax or Bak) they initiate apoptosis. BH3-only proteins are intrinsically disordered and fold and bind into a groove provided by their cognate receptor Bcl-2 family proteins. Our detailed molecular understanding of BH3-only protein action has aided the development of novel chemical entities that initiate cell death by mimicking the properties of BH3-only proteins.
仅含B细胞淋巴瘤-2（Bcl-2）同源结构域3（BH3）的蛋白被认为是Bcl-2家族的成员，尽管它们与具有多个BH基序的促生存或促凋亡Bcl-2蛋白（如Bcl-2或Bax）在序列或结构上几乎没有相似性。它们更适合被视为一个独立的进化实体。综合来看，生物物理、生化、细胞生物学和动物研究的结果，以及结构研究，阐明了这些蛋白的功能和作用机制。它们通过拮抗促生存Bcl-2蛋白或直接激活促凋亡Bcl-2蛋白（Bax或Bak）来启动细胞凋亡。仅含BH3的蛋白本质上是无序的，会折叠并结合到其同源受体Bcl-2家族蛋白提供的凹槽中。我们对仅含BH3蛋白作用的详细分子理解，有助于开发通过模拟仅含BH3蛋白的特性来引发细胞死亡的新型化学实体。
